Elshaarawy Omar, Alquzi Shami Hasan M, Piecha Felix, Rausch Vanessa, Mueller Johannes, Mueller Sebastian
Center for Alcohol Research, University of Heidelberg, Heidelberg, BW, Germany.
Department of Gastroenterology, Liver Unit, Liverpool University Hospitals Foundation Trust, University of Liverpool, Liverpool, UK.
Hepat Med. 2025 Sep 11;17:91-104. doi: 10.2147/HMER.S541039. eCollection 2025.
Liver stiffness (LS) assesses liver fibrosis, while spleen stiffness (SS) is a promising marker for portal hypertension (PH), reflecting blood flow and vascular resistance. However, the response of LS and SS to vasoactive drugs is unclear. This study evaluates the effects of various PH-lowering drugs on LS and SS in a rat cirrhosis model.
In this study, cirrhosis was induced in 43 male Wistar rats (8 weeks old) via intraperitoneal thioacetamide (TAA) injections (200 mg/kg, twice weekly for six weeks). Rats were divided into six groups: control (sodium chloride), metoprolol, udenafil, enalapril, terlipressin, and carvedilol. LS and SS were measured using μFibroscan. Mean arterial pressure (MAP), heart rate (HR), and portal vein pressure (PVP) were continuously monitored. Drugs were administered systemically, with data collected at 0, 15, and 30 minutes.
TAA-treated rats exhibited significantly higher LS and SS compared to controls (22.1 vs 4.2 kPa and 53.7 vs 27.7 kPa; P < 0.001). Changes in LS and SS correlated with PVP (r = 0.670 for LS and r = 0.867 for SS; P < 0.01). Metoprolol, udenafil, enalapril, and carvedilol significantly reduced PVP (22-34%, P < 0.05), accompanied by decreases in LS and SS (13-37%, P < 0.05). Terlipressin did not reduce LS or SS, likely due to opposing effects of increased MAP and reduced PVP.
In conclusion, combined LS and SS measurements may provide valuable non-invasive insights into patient responses and adherence to PH-lowering therapies.
肝脏硬度（LS）用于评估肝纤维化，而脾脏硬度（SS）是门静脉高压（PH）的一个有前景的标志物，反映血流和血管阻力。然而，LS和SS对血管活性药物的反应尚不清楚。本研究评估了各种降低门静脉高压药物对大鼠肝硬化模型中LS和SS的影响。
在本研究中，通过腹腔注射硫代乙酰胺（TAA）（200mg/kg，每周两次，共六周）诱导43只8周龄雄性Wistar大鼠发生肝硬化。大鼠分为六组：对照组（氯化钠）、美托洛尔、伐地那非、依那普利、特利加压素和卡维地洛。使用μFibroscan测量LS和SS。持续监测平均动脉压（MAP）、心率（HR）和门静脉压力（PVP）。药物全身给药，在0、15和30分钟收集数据。
与对照组相比，TAA处理的大鼠表现出显著更高的LS和SS（分别为22.1 vs 4.2kPa和53.7 vs 27.7kPa；P<0.001）。LS和SS的变化与PVP相关（LS的r = 0.670，SS的r = 0.867；P<0.01）。美托洛尔、伐地那非、依那普利和卡维地洛显著降低了PVP（22 - 34%，P<0.05），同时LS和SS也降低（13 - 37%，P<0.05）。特利加压素没有降低LS或SS，可能是由于MAP升高和PVP降低的相反作用。
总之，联合测量LS和SS可能为患者对降低门静脉高压治疗的反应和依从性提供有价值的非侵入性见解。
